Method for automated formulation process for production of radiopharmaceutical injection medicine and evaluation thereof

Abstract

A method of automated formulation process for radiopharmaceutical injection medicine, including preparation for process control and calculation for formulation control, wherein the preparation steps for process control includes measuring radioactivity and size of radiopharmaceutical materials, determining measurement time and calibration time, measuring pH value and impurity percentage of radiopharmaceutical raw materials. By means of input of parameters measured and calculation of the volume of injection solvent and pH value, finished product of injection medicine is obtained when the pH value reaches 6.5, and the finished product is dispensed into the sterile bottles.

1 . A method for automated formulation process and evaluation of a radiopharmaceutical injection medicine comprising:
 (a) Steps of preparation process:   measuring radioactivity of radiopharmaceutical materials;   measuring volume of radiopharmaceutical materials;   determining measurement time of radioactivity;   determining calibration time of radiopharmaceutical injection;   measuring pH value of radiopharmaceutical materials;   measuring the percentage of impurities of radionuclide;   (b) Steps of calculation and measurement for formulation control comprising:   calculating coefficient X, Y, and F for preparation;   calculating volume of benzyl alcohol;   calculating volume of saline;   calculating volume of injection solvent;   measuring pH value of mixed product;   (c) Repeat steps (a) and steps (b) until the pH value reach 6.5;   (d) Mix the radiopharmaceutical materials with the volume in step (a) and the solvent in step (b) with volumes of V b , V n , V j  to produce finish product;   (e) Dispensing the product into sterile bottles.   
   
   
       2 . A method according to  claim 1 , the coefficient X is calculated by:
     X =EXP (−( LN (2)/73.5)×( Tc−Tm )), wherein  Tc  is calibration time and  Tm  is measurement time.   
   
   
       3 . A method according to  claim 1 , the volume of benzyl alcohol is V b =(0.99 V o +V f )×0.009, wherein V o  indicates the volume of the radiopharmaceutical materials, and V f  indicates total volume of benzyl alcohol preparation solvent. 
   
   
       4 . A method according to  claim 1 , the volume of saline is V n =(0.99 V o +Vf)×0.8333, wherein V o  indicates the volume of the radiopharmaceutical materials and V f  indicates the total volume of preparation solvent. 
   
   
       5 . A method according to  claim 1 , the total volume of preparation solvent is V f =(A 0 F/Y)×6−0.99 V o , wherein A 0  indicates the radioactivity, V o  indicates the volume of the radiopharmaceutical materials, F indicates the correction function of the impurities of the nuclide, and Y indicates the activity of the product of each bottle at calibration time.